Dual chamber pacing systems operating in the multi-programmable, VDD, DDD and DDDR pacing modes have been widely adopted in implantable dual chamber pacemakers and certain implantable cardioverter/defibrillators (ICDs) for providing atrial and ventricular synchronized pacing on demand. A DDD pacemaker implantable pulse generator (IPG) includes an atrial sense amplifier to detect atrial depolarizations or P-waves in the right atrium (RA) and generate an atrial sense event (A-EVENT) signal, a ventricular sense amplifier to detect ventricular depolarizations or R-waves in the right ventricle (RV) and generate a ventricular sense event (V-EVENT) signal, atrial and ventricular pacing pulse generators providing atrial and ventricular pacing (A-PACE and V-PACE) pulses, respectively, and an operating system governing pacing and sensing functions. If the atria fail to spontaneously beat within a pre-defined time interval (atrial escape interval), the pacemaker supplies an A-PACE pulse to the RA through an appropriate lead system. The IPG supplies a V-PACE pulse to the RV through an appropriate lead system at the time-out of an AV delay timed from a preceding A-EVENT or generation of an A-PACE pulse unless a non-refractory V-EVENT is generated in response to an R-wave during the AV delay. Such AV synchronous DDD pacemakers have the capability of tracking the patient's natural sinus rhythm and preserving the hemodynamic contribution of the atrial contraction over a wide range of heart rates.
AAV synchronous DDD pacemaker can operate in or be programmed to operate in the VDD mode when the atria function in a normal sinus rhythm between a programmed lower rate limit (LRL) and a programmmed upper rate limit (URL). Thus, the atria are not paced in the VDD pacing mode.
The rate-adaptive DDDR and VDDR pacing mode functions in the above-described manner but additionally provides rate modulation of a pacing escape interval between the programmable LRL and URL as a function of a physiologic signal or rate control parameter (RCP) developed by one or more physiologic sensors and related to the need for cardiac output. Reliance on the intrinsic atrial heart rate is preferred if it is appropriately between the URL and the programmed lower rate. At times when the intrinsic atrial rate is inappropriately high, a variety of “mode switching” schemes for effecting switching between tracking modes and non-tracking modes (and a variety of transitional modes) based on the relationship between the atrial rate and the sensor derived pacing rate have been proposed as exemplified by commonly assigned U.S. Pat. No. 5,144,949, incorporated herein by reference in its entirety.
The VDD, DDD and DDDR pacing modes were initially perceived to be of greatest benefit to cardiac patients whose hearts have an intact sinoatrial (SA) node that generates the atrial depolarizations detectable as P-waves, but also suffer defective A-V conduction, or AV block, wherein the ventricles fail to depolarize in synchrony with the atria. The RV is paced in the DDD pacing mode in synchrony with the atria after a timed out AV delay and is generally adequate to restore cardiac output for sedentary patients. Active patients with Sick Sinus Syndrome (SSS) have an intrinsic atrial rate that can be sometimes appropriate, sometimes too fast, and sometimes too slow. For SSS patients, the DDDR pacing mode provides some relief by pacing the atria and ventricles at a physiologic rate determined by an algorithm responsive to the RCP indicative of the patient's metabolic needs.
A loss of A-V electrical and mechanical synchrony can result in series of asynchronous atrial and ventricular depolarizations at independent rates that periodically result in an atrial depolarization that closely follows a ventricular depolarization. When this occurs, the left atrium (LA) contracts against a closed mitral valve, resulting in impeded venous return from the pulmonary vasculature due to increased atrial pressure and possibly even retrograde blood flow into the pulmonary venous circulation. As a result, the volume and pressure in the pulmonary venous circulation rise. Increased pulmonary pressures may lead to pulmonary congestion and dyspnea. Distension of the pulmonary vasculature may be associated with peripheral vasodilation and hypotension. In addition, the concomitant atrial distension is associated with increased production of atrial natriuretic factor and increases the susceptibility to atrial arrhythmias and possibly rupture of the atrial wall. Finally, turbulence and stagnation of blood within the atrium increase the risk of thrombus formation and subsequent arterial embolization. Maintenance of AV mechanical synchrony is therefore of great importance as set forth in greater detail in commonly assigned U.S. Pat. No. 5,626,623, incorporated herein by reference in its entirety.
Although DDD and DDDR pacing systems were initially offered to treat patients hearts exhibiting A-V conduction defects as described above, the value of dual chamber DDD or DDDR cardiac pacing treatment of patients suffering from HOCM (Hypertrophic Obstructive Cardiomyopathy) has been recognized in the literature. See, for example, “Permanent Pacing As Treatment For Hypertrophic Cardiomyopathy,” by Kenneth M. McDonald et al., American Journal of Cardiology, Vol. 68, pp. 108-110, Jul. 1991. HOCM is characterized by a narrowed left ventricular outflow tract (LVOT), which causes a significant increase in the left ventricular end systolic pressure. The narrowed LVOT is caused by an increased thickness of the interventricular septum that obstructs blood flow out of the LV during systole, the time of cardiac ejection. Studies have indicated that patients suffering from HOCM may benefit from a specific mode of DDD pacing, wherein a V-PACE is delivered to the RV apex or septal wall in carefully timed AV synchrony with the preceding A-EVENT sensed in the RA or the preceding A-PACE delivered in the RA. Pacing the RV apex before spontaneous atrio-ventricular conduction activates the ventricles is understood to alter the ventricular septal activation pattern. Since the RV is caused to contract first, it pulls the septum toward the RV thereby reducing the LVOT obstruction.
The prior art techniques for AV synchronous pacing of HOCM patients, e.g., those disclosed in U.S. Pat. No. 5,340,361, recognize the necessity to periodically evaluate the pacing AV delay. The patient's intrinsic AV delay generally will change with heart rate, i.e., from rest to exercise. Moreover, simultaneous drug treatment such as beta blockers may also modify the intrinsic AV delay and require renewed evaluation of the AV delay. The importance of periodically making an accurate determination of the optimized pacing AV delay thus takes on significance. If the pacing AV delay is adjusted to a value that is too short, in order to ensure complete ventricular capture, the atrial contribution to ventricular filling may be compromised. However, if the pacing AV delay is adjusted to too great a value, ventricular capture is compromised, and there may be episodes of no ventricular pacing or the ventricular pace may not contribute the best possible reduction of the LVOT obstruction. Accordingly, it is important in this therapy to be able to continuously or periodically adjust the pacing AV delay to optimize it for HOCM therapy. Commonly assigned U.S. Pat. Nos. 5,534,506, 5,626,620, 5,626,623, 5,716,383, and 5,749,906 disclose ways of optimizing the pacing AV delay for pacing hearts exhibiting HOCM.
It has also been proposed that various conduction disturbances involving both bradycardia and tachycardia of a heart chamber could benefit from pacing pulses applied at multiple pace/sense electrode sites positioned in or about a single heart chamber or in the right and left heart chambers in synchrony with a depolarization which has been sensed at least one of the pace/sense electrode sites. It is believed that atrial and left ventricular cardiac output can be significantly improved when left and right chamber synchrony is restored, particularly in patients suffering from dilated cardiomyopathy (DCM) and congestive heart failure (CHF).
CHF is defined generally as the inability of the heart to deliver enough blood, i.e., to supply sufficient cardiac output, to the peripheral tissues to meet metabolic demands. Frequently CHF is manifested by left ventricular dysfunction (LVD), but it can have a variety of sources including HOCM, different conduction defects, cardiomyopathies, etc. The natural electrical activation system through the heart involves sequential events starting with the sino-atrial (SA) node, and continuing through the atrial conduction pathways of Bachmann's bundle and internodal tracts at the atrial level, followed by the atrio-ventricular (AV) node, Common Bundle of His, right and left bundle branches, and final distribution to the distal myocardial terminals via the Purkinje fiber network as shown in FIG. 1.
FIG. 1 is an illustration of transmission of the cardiac depolarization waves through the RA, LA, RV and LV of heart 10 in a normal electrical activation sequence at a normal heart rate with the conduction times exhibited thereon in seconds. The cardiac cycle commences normally with the generation of the depolarization impulse at the SA Node in the right atrial wall and its transmission through the atrial conduction pathways of Bachmann's Bundle and the Internodal Tracts at the atrial level into the left atrial septum. The RA depolarization wave reaches the AV node and the atrial septum within about 40 msec and reaches the furthest walls of the RA and LA within about 70 msec, and the atria complete their contraction as a result of the electrical activation. The aggregate RA and LA depolarization wave appears as the P-wave of the PQRST complex when sensed across external ECG electrodes and displayed. The component of the atrial depolarization wave passing between a pair of unipolar or bipolar pace/sense electrodes, respectively, located on or adjacent the RA or LA is also referred to as a sensed P-wave. Although the location and spacing of the external ECG electrodes or implanted atrial pace/sense electrodes has some influence, the normal P-wave width does not exceed 80 msec in width as measured by a high impedance sense amplifier coupled with such electrodes. A normal near field P-wave sensed between closely spaced bipolar pace/sense electrodes and located in or adjacent the RA or the LA has a width of no more than 60 msec as measured by a high impedance sense amplifier.
The depolarization impulse that reaches the AV Node is distributed inferiorly down the bundle of His in the intraventricular septum after a delay of about 120 msec. The depolarization wave reaches the apical region of the heart about 20 msec later and is then travels superiorly though the Purkinje Fiber network over the remaining 40 msec. The aggregate RV and LV depolarization wave and the subsequent T-wave accompanying re-polarization of the depolarized myocardium are referred to as the QRST portion of the PQRST cardiac cycle complex when sensed across external ECG electrodes and displayed. When the amplitude of the QRS ventricular depolarization wave passing between a bipolar or unipolar pace/sense electrode pair located on or adjacent the RV or LV exceeds a threshold amplitude, it is detected as a sensed R-wave. Although the location and spacing of the external ECG electrodes or implanted ventricular pace/sense electrodes has some influence, the normal R-wave width does not exceed 80 msec in width as measured by a high impedance sense amplifier. A normal near field R-wave sensed between closely spaced bipolar pace/sense electrodes and located in or adjacent the RV or the LV has a width of no more than 60 msec as measured by a high impedance sense amplifier. The typical normal conduction ranges of sequential activation are also described in the article by Durrer et al., entitled “Total Excitation of the Isolated Human Heart”, in CIRCULATION (Vol. XLI, pp. 899-912, June 1970).
This normal electrical activation sequence becomes highly disrupted in patients suffering from advanced CHF and exhibiting an intra-atrial conduction defect (IACD) and/or an interventricular conduction defect (IVCD). A common type of intra-atrial conduction defect is known as or intra-atrial block (IAB), a condition where the atrial activation is delayed in getting from the RA to the LA. In left bundle branch block (LBBB) and right bundle branch block (RBBB), the activation signals are not conducted in a normal fashion along the right or left bundle branches respectively. Thus, in a patient with bundle branch block, the activation of the RV and the LV is slowed, and the QRS is seen to widen due to the increased time for the activation to traverse the conduction path. These conduction defects exhibit great asynchrony between the RV and the LV due to conduction disorders along the Bundle of His, the Right and Left Bundle Branches or at the more distal Purkinje Terminals. Typical intra-ventricular peak-peak asynchrony can range from 80 to 200 msec or longer. In RBBB and LBBB patients, the QRS complex is widened far beyond the normal range to from >120 msec to 250 msec as measured on surface ECG. This increased QRS width demonstrates the lack of synchrony of the right and left ventricular depolarizations and contractions.
AV synchronized pacing of CHF hearts exhibiting DCM (CHF/DCM hearts) and lack of ventricular synchrony due to an IVCD of BBB condition do not necessarily benefit from the typically long AV delay that is determined to be optimal for HOCM patients. Frequently, CHF/DCM hearts exhibit intrinsic A-V (alternatively referred to as P-Q) conduction intervals or delays between 180 ms-260 ms with LBBB patterns or IVCD, and widened QRS complexes >120 ms, and also exhibit A-V conduction defects, including 1° AV Block (AVB). In time, the 1° AV Block can degenerate to 2° AV Block or 3° AV Block. Widened QRS Complexes (>120 ms), caused either by LBBB, IVCD, or RV paced evoked response, represent a significant delay in LV electrical activation and thus a significant delay in LV mechanical activation.
Optimal AV delay timing is obtained when the onset of LV contraction occurs immediately upon completion of the LA contribution (Left Atrial Kick) in late diastole. At this moment, the LV filling (preload) is maximum, and the Frank-Starling Relationship between LV stretch and LV contraction is the greatest. This will result in maximum LV stroke volume ejection, and thus maximum Cardiac Index/Cardiac Output to be realized. To realize this exact A-V Sequential timing, the AV delay must be fully optimized.
Any delay between the completion of atrial contribution and the start of LV contraction can lead to “Pre-Systolic” mitral regurgitation, resulting in loss of effective LV filling and thus loss of LV stroke volume and reduced cardiac output. In addition, a too long AV delay reduces the diastolic time available for proper LVFT as observed on the diastolic Transmitral Inflow Pattern, resulting in a fusion of the transmitral inflow rapid filling phase (E wave) and active filling phase (A wave) of the Mitral Flow Relationship. A short, optimized AV delay, however, will allow maximum de-fusion of E and A waves, and a maximum LVFT to be realized at any given heart rate, contributing to increased cardiac output.
Thus, cardiac depolarizations that naturally occur in one upper or lower heart chamber are not conducted in a timely fashion either within the heart chamber or to the other upper or lower heart chamber diseased hearts exhibiting LVD and CHF. In such cases, the right and left heart chambers do not contract in optimum synchrony with each other, and cardiac output suffers due to the conduction defects. In addition, spontaneous depolarizations of the LA or LV occur at ectopic foci in these left heart chambers, and the natural activation sequence is grossly disturbed. In such cases, cardiac output deteriorates because the contractions of the right and left heart chambers are not synchronized sufficiently to eject blood therefrom. Hearts evidencing CHF with and without LVD have reduced ejection fraction from the LV thereby reducing stroke volume and promoting pulmonary edema limiting the patient's ability to exercise as described in commonly assigned U.S. Pat. No. 6,129,744. Furthermore, significant conduction disturbances between the RA and LA can result in left atrial flutter or fibrillation.
A number of proposals have been advanced for providing pacing therapies to alleviate heart failure conditions and restore synchronous depolarization and contraction of a single heart chamber or right and left, upper and lower, heart chambers as described in detail in the above referenced '744 patent and in commonly assigned U.S. Pat. Nos. 5,403,356, 5,797,970 and 5,902,324 and in U.S. Pat. Nos. 5,720,768 and 5,792,203. The proposals appearing in U.S. Pat. Nos. 3,937,226, 4,088,140, 4,548,203, 4,458,677, 4,332,259 are summarized in U.S. Pat. Nos. 4,928,688 and 5,674,259. The advantages of providing sensing at pace/sense electrodes located in both the right and left heart chambers is addressed in the '688 and '259 patents, as well as in U.S. Pat. Nos. 4,354,497, 5,174,289, 5,267,560, 5,514,161, and 5,584,867.
The medical literature also discloses a number of approaches of providing bi-atrial and/or bi-ventricular pacing as set forth in: Daubert et al., “Permanent Dual Atrium Pacing in Major Intra-atrial Conduction Blocks: A Four Years Experience”, PACE (Vol. 16, Part II, NASPE Abstract 141, p.885, April 1993); Daubert et al., “Permanent Left Ventricular Pacing With Transvenous Leads Inserted Into The Coronary Veins”, PACE (Vol. 21, Part II, pp. 239-245, January 1998); Cazeau et al., “Four Chamber Pacing in Dilated Cardiomyopathy”, PACE (Vol. 17, Part II, pp. 1974-1979, November 1994); and Daubert et al., “Renewal of Permanent Left Atrial Pacing via the Coronary Sinus”, PACE (Vol. 15, Part II, NASPE Abstract 255, p. 572, April 1992).
Typically, the bi-ventricular pacing systems described in the literature and in patents pace the RV and the LV simultaneously or separated by a programmable V-V pace delay, which is either an RV-LV pace delay or an LV-RV pace delay. Typically, in the prior art, the AV delay is timed out, the first V-PACE is delivered to one of the RV and LV, the V-V pace delay is timed out, and the second V-PACE is delivered to the other of the RV and LV. Or, an A-RV delay and an A-LV delay are started on the atrial pace or atrial sense event, and the RV-PACE and LV-PACE pulses are delivered to the RV and LV, in the predetermined sequence, when they time out. All of these delays are typically made programmable.
In the above-referenced '324 patent, an AV synchronous pacing system is disclosed providing three or four heart chamber pacing through pace/sense electrodes located in or adjacent one or both of the RA and LA and in or adjacent to both the RV and LV. One or two paced AV (PAV) delays defined to follow a selected one or both of the RA-PACE or LA-PACE and sensed AV (SAV) delays are timed from one of the RA-EVENT or the LA-EVENT. A non-refractory RV-EVENT or LV-EVENT detected at the respective RV or LV pace/sense electrodes during the time-out of the prevailing AV delay or V-A escape interval starts a conduction time window (CDW) timer. A LV-PACE or RV-PACE is delivered to the other of the LV or RV pace/sense electrodes at the time-out of the CDW if an LV-EVENT or RV-EVENT is not detected at that site while the CDW times out. The CDW can be set to zero, whereby RV-PACE and LV-PACE pulses are delivered simultaneously to the RV and LV upon time-out of the prevailing AV delay.
Recent findings of studies of such hearts has determined that each CHF/DCM heart has an optimal short AV delay that generates the highest cardiac output and provides the most physiologic hemodynamics as measured using echocardiography. See, “Effect of pacing chamber and atrioventricular delay on acute systolic function of paced patients with congestive heart failure” by Auricchio A, Stellbrink C, et al., CIRCULATION 1999, June 15;99 (23):2993-3001.
Short AV delays in the range of 60 ms-140 ms are typically recommended for bi-ventricular pacing to ensure ventricular capture and appropriate left ventricular filling. The relatively short AV delay is most optimally determined by testing the cardiac hemodynamic performance at differing AV delays.
The pacing regimens provided by these three and four chamber pacing systems are intended to achieve a shortening of the abnormally wide, intrinsically exhibited QRS complex, which is an attribute of most hearts exhibiting CHF with bundle branch block as described above. However, certain hearts exhibiting CHF do not exhibit abnormally wide QRS complexes, and cardiac output is not necessarily improved when bi-ventricular pacing is applied as described above. In fact, the bi-ventricular pacing can unduly widen the resulting evoked QRS complexes.
Moreover, the relatively short AV delays can cause an evoked contraction of the ventricles before the ventricles fill with blood from the atria.